1. Field of the Invention
The present invention relates to topical compositions for reducing, preventing, or reversing damage to the eyes resulting from oxidative stress (dry eye, cataracts, retinal degeneration, etc.), and particularly to antioxidant eye drops containing four nutraceuticals in a carbomer gel carrier.
2. Description of the Related Art
The prevalence of age-related ocular diseases, such as cataract, macular degeneration (AMD) and keratoconjunctivitis sicca (KCS, commonly known as dry eye), increases as populations age. Cataracts account for the majority of reversible age-related vision loss, while AMD is the leading cause of irreversible blindness. KCS, which affects the majority of people over the age of 65, results in significant ocular discomfort and visual dysfunction. While KCS generally does not result in vision loss, KCS, if left untreated, results in painful superficial keratitis that can lead to corneal ulcers or scars.
Age-related diseases are also a growing problem in the veterinary community. Loss of vision from cataracts is the major cause of blindness in dogs and cats. Progressive retinal atrophy with clinical onsets varying from 6 months to 10+ years can also develop in many of these companion pets. These retinal degenerations also have strong genetic links. The onset of dry eye in dogs increases as dogs approach 7-9 years of age. KCS is increased in older female dogs, as compared to male dogs, and is increased in both neutered males and females. In contrast to dogs, the presence of KCS in cats is more subtle.
There is no established pharmaceutical treatment for age-related cataracts, and vision in patients can only be restored by surgery. It has been estimated that the need for cataract surgery can be reduced by 50% by delaying the onset and progression of cataracts by 10 years. The need for a nonsurgical treatment for delaying cataracts is supported by findings that cataract surgery increases the incidence of late AMD. At present, there is also no medical treatment for preventing the onset or reducing the enlargement of geographic atrophy (dry AMD).
The pathogeneses of cataracts and AMD have not been established. However, both are multifactorial diseases with risk factors that include smoking, which is associated with the generation of reactive oxygen species (ROS) and increased tissue iron levels. Dry eye is also a multifactorial disease involving oxidative stress. Smoking also increases the risk of dry eye and exacerbates existing dry eye conditions. Experimentally, increased oxidative damage accompanied by increased levels of iron has been linked to the development and progression of cataracts and AMD. ROS generated in the presence of iron results in the formation of hydroxyl radicals through the Fenton reaction, and also results in mitochondrial dysfunction. Cataracts also develop in patients with hyperferritinemia, an iron disorder associated with increased iron levels. Dysregulation of iron metabolism and iron-handling proteins is also linked to the pathogenesis of AMD, marked by increased chelatable iron observed in the retinal pigmented epithelial cells (RPE) and Bruchs membrane in retinas from AMD patients. Iron overload is also associated with a maculopathy that clinically resembles AMD, including the development and progression of multiple subretinal yellowish-white lesions and RPE cell atrophy in patients with aceruloplasminemia.
Studies indicate that targeting oxidative pathways associated with these age related diseases is therapeutically beneficial. Most formulations containing natural antioxidant and/or vitamins for the support of antioxidant eye health and the reduction of cataract development are orally administered. For example, the oral clinical administration of a combined formulation of natural antioxidants and omega-3 essential fatty acids significantly improves the subjective symptoms of dry eye, while the oral administration of the AREDS natural antioxidant formulation reduces the risk of progression to advanced AMD by 25%. However, several large clinical studies where the nutraceuticals formulations were orally administered suggest that any observed effect of these antioxidants on cataract development is likely to be small and probably of no clinical or public health significance. ROS can also be reduced by lowering tissue levels of iron, which can generate reactive hydroxyl radicals through the Fenton reaction. Studies using chelating agents to reduce iron levels suggest that ROS may also be beneficially reduced in the lens because patients with β-thalassemia receiving chelation therapy with drugs (such as deferoxamine) have a lower incidence of cataracts. Similarly in rats, cataracts from tobacco smoke exposure were reduced by deferoxamine treatment. Novel multifunctional antioxidants with the ability to independently scavenge free radicals and chelate iron have been shown to also delay both cataract formation and protect the retina against light damage, a model for AMD.
Thus, antioxidant eye drops solving the aforementioned problems is desired.